Glucose sensor package system

ABSTRACT

A glucose sensor package system that includes a glucose sensor and a protective package that indicates exposure to temperature changes to indicate proper temperature control. Also covered are methods of transporting and sterilizing the package. In addition, glucose sensors directed to various sizing and positioning of the electrodes on the glucose sensor are covered.

RELATED APPLICATIONS

This application is a division of Ser. No. 09/501,847, filed Feb. 10,2000, which claims benefits to U.S. Provisional Patent ApplicationSerial No. 60/121,655, filed Feb. 25, 1999, which is herein incorporatedby reference in its entirety, including all attachments.

FIELD OF THE INVENTION

This invention relates to glucose monitor systems and, in particularembodiments, to glucose sensors for use with glucose monitor systems andto the packaging for the glucose sensors. The invention also relates tothe size, shape and positioning of electrodes on a glucose sensor.

BACKGROUND OF THE INVENTION

Over the years, bodily characteristics have been determined by obtaininga sample of bodily fluid. For example, diabetics often test for bloodglucose levels. Traditional blood glucose determinations have utilized apainful finger prick using a lancet to withdraw a small blood sample.This results in discomfort from the lancet as it contacts nerves in thesubcutaneous tissue. The pain of lancing and the cumulative discomfortfrom multiple needle pricks is a strong reason why patients fail tocomply with a medical testing regimen used to determine a change incharacteristic over a period of time. Although non-invasive systems havebeen proposed, or are in development, none to date have beencommercialized that are effective and provide accurate results. Inaddition, all of these systems are designed to provide data at discretepoints and do not provide continuous data to show the variations in thecharacteristic between testing times.

A variety of implantable electrochemical sensors have been developed fordetecting and/or quantifying specific agents or compositions in apatient's blood. For instance, glucose sensors are being developed foruse in obtaining an indication of blood glucose levels in a diabeticpatient. Such readings are useful in monitoring and/or adjusting atreatment regimen which typically includes the regular administration ofinsulin to the patient. Thus, blood glucose readings improve medicaltherapies with semi-automated medication infusion pumps of the externaltype, as generally described in U.S. Pat. Nos. 4,562,751; 4,678,408; and4,685,903; or automated implantable medication infusion pumps, asgenerally described in U.S. Pat. No. 4,573,994, which are hereinincorporated by reference. Typical thin film sensors are described incommonly assigned U.S. Pat. Nos. 5,390,671; 5,391,250;5,482,473; and5,586,553 which are incorporated by reference herein. See also U.S. Pat.No. 5,299,571.

Many of these glucose sensors utilize complex chemical structures and/orreactions that can degrade over time, if maintained under improperconditions. Since sensors may be stored for long periods of time aftermanufacture and prior to use, the sensors must be monitored frequentlyand maintained in areas with a carefully controlled environment. Themonitoring of sensors is particularly difficult once the sensors havebeen sterilized and placed in packages. Often the only way to monitorthe sensors is to pull a sample and remove it from a package. However,this destroys the sterility and results in waste. Also, monitoringsensors that have been shipped to a user are problematic or difficult.

SUMMARY OF THE DISCLOSURE

It is an object of an embodiment of the present invention to provide animproved glucose sensor package system, which obviates for practicalpurposes, the above mentioned limitations.

Embodiments of the present invention are directed to a glucose sensorpackage system that includes a glucose sensor and a protective packagethat indicates proper exposure to sterilization or exposure totemperature changes to indicate proper temperature control. Also coveredare methods of transporting and sterilizing the package. In addition,further embodiments of the glucose sensors are directed to the sizingand positioning of the electrodes on the glucose sensor.

According to an embodiment of the invention, a glucose sensor packagesystem for storing and transporting a glucose sensor includes at leastone glucose sensor, a protective package and at least one temperatureexposure indicator. The protective package has an interior to hold theat least one glucose sensor in the interior of the protective package.The at least one temperature exposure indicator is used to determine ifthe protective package has been exposed to at least one exposuretemperature relative to a predetermined threshold temperature value. Inparticular embodiments, the at least one exposure temperature is abovethe predetermined threshold temperature, and the at least onetemperature exposure indicator indicates when there has been exposure tothe at least one exposure temperature. For instance, the predeterminedthreshold temperature is 75° F. and the at least one exposuretemperature exceeds 75° F., or the predetermined threshold temperatureis 100° F. and the at least one exposure temperature exceeds 100° F. Inother embodiments, the at least one exposure temperature is below thepredetermined threshold temperature, and the at least one temperatureexposure indicator indicates when there has been exposure to the atleast one exposure temperature. For instance, the predeterminedthreshold temperature is 36° F. and the at least one exposuretemperature is below 36° F.

In additional embodiments, the at least one temperature exposureindicator indicates when the at least one exposure temperature relativeto the predetermined threshold temperature existed for a predeterminedperiod of time. For instance, the predetermined period of time can be atleast 10 minutes, or at least 60 minutes. In other embodiments, theperiod of time is established as a function of a magnitude of adifference between the at least one exposure temperature and thepredetermined threshold temperature.

In particular embodiments, the at least one temperature exposureindicator is attached to the protective package. For instance, the atleast one temperature exposure indicator may be attached to the interiorof the protective package or an exterior of the protective package. Infurther embodiments, the at least one temperature exposure indicator iscontained within the protective package, or attached to the glucosesensor. In preferred embodiments, the at least one temperature exposureindicator is a sticker. Other embodiments are directed to a method oftransporting the glucose sensor in a package system.

According to another embodiment of the invention, a glucose sensorpackage system for storing and transporting a glucose sensor includes atleast one glucose sensor, a protective package, and at least onetemperature exposure indicator. The protective package has an interiorwithin which the at least one glucose sensor is disposed, and anexterior. The at least one temperature exposure indicator has first andsecond states, of which the first state indicates that the protectivepackage has not been exposed to at least one exposure temperaturerelative to a predetermined threshold temperature value, and the secondstate indicates that the protective package has been exposed to the atleast one exposure temperature. The at least one temperature exposureindicator, in particular embodiments, is attached to the interior of theprotective package or the exterior of the protective package, iscontained within the protective package, or is attached to the glucosesensor.

In further particular embodiments, the glucose sensor package systemincludes a plurality of glucose sensors, each of which is enclosedwithin a separate package. The plurality of separately packaged glucosesensors in turn are disposed within the interior of the protectivepackage. In more specific embodiments, the glucose sensor package systemincludes a plurality of the at least one temperature exposureindicators, each of which is attached to one of the separate packages.

In further embodiments, the glucose sensor package system includes aplurality of the at least one temperature exposure indicators, each ofwhich provides an indication of exposure to at least one exposuretemperature relative to a different predetermined threshold temperaturevalue. These embodiments afford more precise indications of a maximumtemperature to which the package system has been exposed.

Another embodiment of the present invention is directed to a method oftransporting a glucose sensor. The method includes the steps ofproviding at least one glucose sensor. Providing a protective packagehaving an interior. Holding the at least one glucose sensor in theinterior of the protective package. Using at least one temperatureexposure indicator to determine if the protective package has beenexposed to at least one exposure temperature relative to a predeterminedthreshold temperature value.

A further embodiment of the present invention is directed to a method oftransporting a glucose sensor, the method including the steps ofproviding a glucose sensor package system. The package system includingat least one glucose sensor, a protective package having an interiorwithin which the at least one glucose sensor is disposed and anexterior, and at least one temperature exposure indicator having firstand second states. Transporting the glucose sensor package system, andobserving the state of the at least one temperature exposure indicatorto determine if the protective package has been exposed to the at leastone exposure temperature during transport.

Additional embodiments of the method employ a glucose sensor packagesystem that includes a plurality of the at least one temperatureexposure indicators, each of which provides an indication of exposure toat least one exposure temperature relative to a different predeterminedthreshold temperature value. In these embodiments, the observing stepincludes an observation of the state of each of the at least onetemperature exposure indicators to determine if the protective packagehas been exposed to at least one exposure temperature relative to atleast one of the different predetermined threshold values.

Another embodiment of the present invention is directed to a glucosesensor package system for sterilizing a glucose sensor using electronbeam sterilization, the system including at least one glucose sensor, aprotective package, and at least one radiation exposure indicator. Theprotective package has an interior to hold the at least one glucosesensor in the interior of the protective package. The at least oneradiation exposure indicator is used to determine if the protectivepackage has been exposed to a predetermined exposure level of electronbeam sterilization. For example, preferred embodiments have thepredetermined exposure level above 2.0 Mrad. Other embodiments have thepredetermined exposure level less than or equal to 5.0 Mrad or above 0.5Mrad. In further embodiments, the at least one radiation exposureindicator indicates that the predetermined exposure level existed for aperiod of time.

In particular embodiments, the at least one radiation exposure indicatoris attached to the protective package. For example, the at least oneradiation exposure indicator may be attached to the interior of theprotective package, or an exterior of the protective package. In otherembodiments, the at least one radiation exposure indicator may becontained within the protective package. In further embodiments, theradiation exposure indicator may be attached to the glucose sensor.Preferably, the at least one radiation exposure indicator is a sticker.Other embodiments are directed to a method of sterilizing the glucosesensor.

Still additional embodiments are directed to a glucose sensor includinga substrate, a working electrode including at least one enzyme and beingcoupled to the substrate, a counter electrode coupled to the substrate,and a reference electrode coupled to the substrate. In preferredembodiments, the counter electrode is formed larger than the workingelectrode, and the working electrode is formed larger than the referenceelectrode. In still further embodiments, the working electrode is placedbetween counter electrode and the reference electrode. In additionalembodiments, the glucose sensor also includes at least one attachedtemperature exposure indicator.

Packaged glucose sensors as described above are also provided inaccordance with further embodiments. Further embodiments include atleast one temperature exposure indicator attached to the packagingand/or to the glucose sensor.

Other features and advantages of the invention will become apparent fromthe following detailed description, taken in conjunction with theaccompanying drawings which illustrate, by way of example, variousfeatures of embodiments of the invention.

BRIEF DESCRIPTION OF THE DRAWINGS

A detailed description of embodiments of the invention will be made withreference to the accompanying drawings, wherein like numerals designatecorresponding parts in the several figures.

FIG. 1 is a is a perspective view illustrating a subcutaneous glucosesensor insertion set and glucose monitor device embodying the novelfeatures of the invention;

FIG. 2 is an enlarged longitudinal vertical section taken generally onthe line 2—2 of FIG. 1;

FIG. 3 is an enlarged longitudinal sectional of a slotted insertionneedle used in the insertion set of FIGS. 1 and 2;

FIG. 4 is an enlarged transverse section taken generally on the line 4—4of FIG. 3;

FIG. 5 is an enlarged transverse section taken generally on the line 5—5of FIG. 3;

FIG. 6 is an enlarged fragmented sectional view corresponding generallywith the encircled region 6 of FIG. 2;

FIG. 7 is an enlarged transverse section taken generally on the line 7—7of FIG. 2;

FIGS. 8a-c are perspective views, partially cut away, of embodiments ofglucose sensor package systems including a protective package, a glucosesensor and a temperature exposure indicator, with the temperatureexposure indicator attached to the exterior of the protective package,the interior of the protective package, and the glucose sensor,respectively;

FIG. 9 is an exploded view of a glucose sensor package system thatincludes a plurality of individually packaged glucose sensors alldisposed within a protective package, with each of the individuallypackaged glucose sensors having an attached temperature exposureindicator; and

FIG. 10 is a perspective view of a glucose sensor package systemincluding a plurality of temperature exposure indicators;

FIG. 11 is a view of a label with multiple temperature exposureindicators in accordance with an embodiment of the present invention;

FIG. 12 is a view of a portion of an “instructions for use” inaccordance with an embodiment of the present invention;

FIG. 13 is a top plan view of a sensor in accordance with an embodimentof the present invention;

FIG. 14 is a top plan view of the sensor conductors shown in FIG. 13;and

FIG. 15 is an enlarged, partial top plan view of the electrodes of thesensor shown in FIG. 13.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

As shown in the drawings for purposes of illustration, the invention isembodied in a glucose monitor system that is coupled to a subcutaneousglucose sensor set to provide continuous data recording of the sensorreadings for a period of time. In preferred embodiments of the presentinvention, the glucose sensor and glucose monitor are for determiningglucose levels in the blood and/or bodily fluids of the user. However,it will be recognized that further embodiments of the invention may beused to determine the levels of other analytes or agents,characteristics or compositions, such as hormones, cholesterol,medications concentrations, viral loads (e.g., HIV), or the like. Inother embodiments, the glucose monitor may also include the capabilityto be programmed to take data at specified time intervals or calibratedusing an initial data input received from an external device. Theglucose monitor and glucose sensor are primarily adapted for use insubcutaneous human tissue. However, still further embodiments may beplaced in other types tissue, such as muscle, lymph, organ tissue,veins, arteries or the like, and used in animal tissue. Embodiments mayrecord sensor readings on an intermittent, near continuous or continuousbasis.

Due to the use of enzyme materials, or other complex chemistries, on theelectrodes of the glucose sensor, it is important to maintain theglucose sensor at lower temperatures for storage and transport prior touse. Preferably, the glucose sensor is stored in a controlledtemperature range of 2 to 24° C. (or 36 to 75° F.) to provide a minimumlong term storage time of 6 months to 2 years. However, shorter storagetimes of 1 month or longer storage times of 5 years (or more) may beused. In addition, glucose sensors are preferably designed to withstand1 hour of 45° C. (or 113° F.) without substantial de-nature of theglucose sensor enzyme or chemistries.

The best approach to assure proper temperature control is to refrigeratethe glucose sensors, but not freeze them. Preferably, the glucosesensors should be shipped in temperature controlled vehicles or inindividual packages that provide temperature control duringtransportation, such as with a cold pack, sufficient insulation tomaintain temperature after removal from refrigerated storage, or thelike. It is anticipated that transportation may take anywhere from a fewhours to three days for the glucose sensors to arrive at their intendeddestination, and the temperature must be maintained below apredetermined temperature threshold during this period. In alternativeembodiments, other possibly temperature sensitive materials used in theglucose sensor may also drive the selection of a temperature range orlevel.

To satisfy this temperature control need, embodiments of the glucosesensor and package are augmented with at least one temperature exposureindicator, such as a temperature sensitive sticker, to indicate if theglucose sensor has been exposed to excessive temperatures or has been atelevated temperatures for a predetermined period of time. The indicator,such as a dot, plate, sticker, packet, or the like, comprises atemperature-sensitive material that turns color upon exposure toelevated temperatures. Such temperature-sensitive materials are wellknown to those skilled in the art and are readily availablecommercially. Typically, temperature exposure indicators can be obtainedfrom Wahl Instruments, Inc. of Culver City Calif. (Part No. 442-100F),United Desiccants/Humidial of Colton, Calif. (Part No. HD11LC43), or thelike.

In preferred embodiments, the temperature exposure indicator turns froma white (or slight gray) to a dark gray or black after exposure toelevated temperatures. However, in alternative embodiments, other colorcombinations may be used. If the color change does not match the correcttemperature control color, the user knows from an “instructions for use”(see FIG. 12), which preferably are supplied with the glucose sensor,not to use the glucose sensor. Preferably, the temperature exposureindicator (320, 430, 530, 600, 602) is on the exterior of the packagingto minimize any potential for contamination or reaction with thetemperature indicator materials with the glucose sensor (see FIGS. 8band 9-11). However, in alternative embodiments, the temperature exposureindicator 320 can be placed on the interior of the package (see FIG. 8a)if formed out of materials that will not interact with the glucosesensor, or if the temperature exposure indicator is contained in asealed package that will prevent interaction with the glucose sensor. Infurther embodiments, multiple temperature exposure indicators on thepackaging can be used (see FIGS. 10 and 11). Still further embodimentsutilize temperature exposure indicators 600 that indicate exposures to arange of temperatures, such as a plurality of discrete temperatureexposure indicators that are sensitive to particular temperatures (seeFIG. 11).

According to further embodiments, the temperature exposure indicatorindicates when the glucose sensor has been exposed to an exposuretemperature exceeding a predetermined temperature, for example atemperature exceeding 100° F. (or 38° C.), for a predetermined period oftime or longer, for example longer than 60 minutes, to indicate thatpossible degradation of the glucose materials may have occurred due toelevated temperature exposure. Alternative embodiments can indicate achange after exposure to elevated temperatures with respect to thepredetermined temperature for different time periods, for example aslittle as a few seconds if very sensitive materials are used or aspecific threshold must not be exceeded, or as long as 6 hours ifgenerally temperature insensitive materials or bettertemperature-stabilized materials are used with the selection beingdependent on the temperature tolerance of the glucose sensor.

In addition, other embodiments can include temperature exposureindicators that are sensitive to lower elevated temperatures, such as80° F. (or 27° C.), 75° F. (or 24° C.), or the Like, which is closelyassociated with the preferred maximum long term storage temperature. Iflower temperatures are used, the exposure time required to cause achange in the temperature exposure indicator can be lengthened ifdesired. It is also noted that the temperature exposure indicators mayrespond (by the color change) at more rapid rates for highertemperatures. For instance, a few minutes' exposure to 200° F. (or 93°C.) heat may cause a temperature exposure indicator (that normally takesI hour to change at 100° F. (or 38° C.)) to change and indicatedegradation in the glucose sensor. Proper temperature control assuresthe user that the glucose sensors will operate properly and have notsuffered degradation to the enzyme, or other temperature sensitivematerials, that could effect the safe use of the device.

Thus, in particular embodiments, the temperature exposure indicator canprovide an indication of exposure to exposure temperatures relative tothe predetermined temperature that occur for time periods that vary withthe difference between the exposure temperature and the predeterminedtemperature. That is, the period of time t_(e) is a function F of amagnitude of a difference Δ between the exposure temperature t_(e) andthe predetermined temperature t_(d). Depending on the specifictemperature-sensitive material used in the temperature exposureindicator, the functional relationship can be one of proportionality,e.g., t_(e)=kΔ, with k being a constant that is characteristic of thespecific material; an exponential relationship, e.g., t_(d)=k₁exp(k₂Δ),where k₁ and k₂ are constants; or another functional relationship. Theparticular functional relationship will depend on the specifictemperature-sensitive material employed, and can readily be determinedby the routineer without undue experimentation. In other embodiments,the temperature sensitive material changes immediately upon exposure toa temperature above a specific threshold, such that it changes infractions of a second, seconds or after longer periods.

FIGS. 8a-c illustrate embodiments of a glucose sensor package systemaccording to embodiments of the present invention including a glucosesensor 300, a protective package 310 having an interior 312 and anexterior 314, and a temperature exposure indicator 320. In FIG. 8a,glucose sensor 300 is disposed in interior 312 of protective package310, and temperature exposure indicator 320 is attached to the interior312 of protective package 310. In FIG. 8b, glucose sensor 300 islikewise disposed within interior 312, but a temperature exposureindicator 320 is attached to the exterior 314 of protective package 310.In FIG. 8c, a temperature exposure indicator 320 is attached directly toglucose sensor 300, which in turn is disposed within interior 312 ofprotective package 310.

In FIG. 9, glucose sensor package system 400 includes a plurality ofglucose sensors 410 each packaged in a separate package 412. Thepackaged glucose sensors 410 in turn are disposed within the interior422 of protective package 420. A separate temperature exposure indicator430 is affixed to each package 412. If desired, separate temperatureexposure indicators can also be affixed to the protective package 420 ina manner similar to that described in connection with FIGS. 8a-b.

In FIG. 10, a glucose sensor package system 500 includes a protectivepackage 510 having an interior 512 within which glucose sensor 520 isdisposed. A plurality of temperature exposure indicators 530 areattached to the protective package 510. Each of the plurality oftemperature exposure indicators 530 preferably provides an indication ofexposure to an exposure temperature relative to a differentpredetermined temperature value. For example, a first temperatureexposure indicator can indicate exposure to an exposure temperaturerelative to 80° F. (or 27° C.), 75° F. (or 24° C.), or the like, asecond temperature exposure indicator can indicate exposure to anexposure temperature relative to 100° F., a third temperature exposureindicator can indicate exposure to an exposure temperature relative to120° F. (or 49° C.), and so on. Further particular embodiments alsoinclude temperature exposure indicators that provide an indication thatthe exposure temperature relative to the predetermined temperatureexisted for a predetermined period of time.

Preferred embodiments of the glucose sensor are sterilized by electronbeam sterilization with a preferred single dose of 2.0 Mrads (or 20kGy). However, in alternative embodiments, smaller dose levels may beused if sufficient sterilization may be achieved at the lower dose, suchas for example 0.5 Mrads (5 kGy). Larger doses may also be used, if theglucose sensor materials are selected and assembled to withstand dosesup to 5.0 Mrads (50 kGy). The glucose sensors are preferably sterilizedin accordance with “ANSI/AAMI ST31-190 Guideline for Electron BeamRadiation Sterilization of Medical Devices, Method B1” and/or “ISO11137:1995 Sterilization of Health Care Products—Validation and RoutineControl—Gamma and Electron Beam Radiation Sterilization, Dose SelectionMethod 1”, all of which are specifically incorporated by reference. Thesensor materials are carefully selected with regard to housingmaterials, cannula materials, glucose sensor substrate, electrodes,membranes, enzyme chemistry, lubricants, insertion needle materials andthe packaging materials, and manufacturing tolerances to assure theability to withstand electron beam sterilization and the continuedproper operation of the glucose sensor after sterilization. Inalternative embodiments, other radiation sterilization methods, such asgamma radiation, or the like, or other chemical methods, such as ETO, orthe like, may be used.

Preferred embodiments of the glucose sensor with the packaging includeat least one sterilization indicator that indicates when the glucosesensor and packaging have been exposed to an electron beam sterilizationprocedure. The sterilization indicator, such as a dot, plate, sticker,packet, or the like, turns color upon exposure to the electron beam. Inpreferred embodiments, the sterilization indicator turns from a mustardyellow color or orange yellow to a red or reddish orange color aftersterilization. However, in alternative embodiments, other colorcombinations may be used. If the color change does not match the correctsterilization color, the user knows from an “instructions for use” (seeFIG. 12) not to use the glucose sensor. Preferably, the sterilizationindicator is on the exterior of the packaging to minimize any potentialfor contamination or reaction of the sticker materials with the glucosesensor. However, in alternative embodiments, the sterilization indicatormay be placed on the interior of the package if formed out of materialsthat will not interact with the glucose sensor or if the indicator iscontained in a sealed package that will prevent interaction with theglucose sensor. In further embodiments, multiple indicators, orstickers, on the packaging may be used. Typical sterilization indicatorsmay be obtained from NAMSA Products of Kennesaw, Ga. (Part No. CPI-RO3).In addition, the sterilization indicators can be attached to thepackaging and/or glucose sensors in a manner similar to that fortemperature exposure indicators as shown in FIGS. 8a-11 and describedabove.

As shown in FIGS. 13-15, further embodiments of the glucose sensor 700are directed towards optimizing the size, shape and orientation of theglucose sensor electrodes that come in contact with the interstitialfluid during glucose sensing. In preferred embodiments, the glucosesensor 700 includes three electrodes (a working electrode 702, a counterelectrode 704 and a reference electrode 706). To optimize theelectrochemistry of the glucose sensing reaction, it is preferred thatthe counter electrode 704 is the largest electrode, the workingelectrode 702 (i.e., the one with enzymes, or the like) is the nextlargest electrode and the reference electrode 706 is the smallestelectrode. Preferably, the counter electrode 704 is as large as possibleand consistent with sensor insertion requirements to minimize pain oninsertion of the sensor into the body of the user. For instance, to fitwithin a 22 gauge needle. However, alternative embodiments may be sizedto fit other gauge needles ranging from 18 gauge to 30 gauge. Inaddition, making the working electrode a different size effects theamount of enzyme that can be placed on the working electrode and affectsthe overall life of the glucose sensor. In further preferredembodiments, it has been found to optimize the current paths and theelectrochemistry to have the working electrode 702 located between thecounter electrode 704 and the reference electrode 706. In additionalembodiments, it is preferred that the electrode (i.e., conductors) havea line width of 50μ to assure good electrical conduction of a sensorsignal. However, smaller widths down to 10μ and anything larger can beused if a sufficient signal accuracy is provided and the sensor can fitwithin a needle as described above.

Additional specific embodiments of the glucose sensor include atemperature exposure indicator as described above attached directly tothe sensor.

Turning again to the figures, the above may be used with the glucosemonitor system 1, in accordance with a preferred embodiments of thepresent invention that includes a subcutaneous glucose sensor set 10,and a glucose monitor 100. The subcutaneous glucose sensor set 10utilizes an electrode-type sensor, as described in more detail below.However, in alternative embodiments, the glucose sensor may use othertypes of sensors, such as chemical based, optical based or the like. Infurther alternative embodiments, the sensors may be of a type that isused on the external surface of the skin or placed below the skin layerof the user. Preferred embodiments of a surface mounted glucose sensorwould utilize interstitial fluid harvested from the skin.

The glucose monitor 100 generally includes the capability to record andstore data as it is received from the glucose sensor 10, and thenincludes either a data port or wireless transmitter for downloading thedata to a data processor 200, computer, communication station, or thelike for later analysis and review. The data processor 200, computer, orthe like, utilizes the recorded data from the glucose monitor todetermine the blood glucose history. Preferably, any port would be waterproof (or water resistant) or include a water proof removable cover. Thepurpose of the glucose monitor system 1 is to provide for better datarecording and testing for various patient conditions utilizingcontinuous or near continuous data recording.

The glucose monitor system 1 also removes inconvenience by separatingthe complicated monitoring process electronics into two separatedevices; a glucose monitor 100, which attaches to the glucose sensor set10; and a data processor 200, computer, communication station, or thelike, which contains the software and programming instructions todownload and evaluate data recorded by the glucose monitor 100. Inaddition, the use of multiple components (e.g., glucose monitor 100 anddata processor 200, computer, communication station, or the like)facilitates upgrades or replacements, since one module, or the other,can be modified or replaced without requiring complete replacement ofthe monitor system 1. Further, the use of multiple components canimprove the economics of manufacturing, since some components mayrequire replacement on a more frequent basis, sizing requirements may bedifferent for each module, different assembly environment requirements,and modifications can be made without affecting the other components.

The glucose monitor 100 takes raw glucose sensor data, such as glucosedata or the like, from the subcutaneous-glucose sensor set 10 andassesses it during real-time and/or stores it for later download to thedata processor 200, computer, communication station, or the like, whichin turn analyzes, displays and logs the received glucose readings.Logged data can be analyzed further for detailed data analysis. Infurther embodiments, the glucose monitor system 1 may be used in ahospital environment or the like. Still further embodiments of thepresent invention may include one or more buttons 122, 124, 126 and 128on the glucose monitor 100 to program the monitor 100, to record dataand events for later analysis, correlation, or the like. In addition,the glucose monitor may include an on/off button 130 for compliance withsafety standards and regulations to temporarily suspend transmissions orrecording. The glucose monitor 100 may also be combined with othermedical devices to combine other patient data through a common datanetwork and telemetry system. In alternative embodiments, the glucosemonitor may be designed as a Holter-type system that includes aHolter-type recorder that interfaces with a glucose monitor, processor,computer, or the like, such as disclosed in U.S. patent application Ser.No. 09/246,661 filed Feb. 5, 1999 and entitled “An Analyte Sensor andHolter-Type Monitor System and Method of Using the Same”, and U.S.patent application Ser. No. 09/377,472 filed Aug. 19, 1999 and entitled“Telemetered Characteristic Monitor System and Method of Using theSame”, which are all herein incorporated by reference.

As shown in FIGS. 1-7, a glucose sensor set 10 is provided forsubcutaneous placement of a flexible sensor 12 (see FIG. 2), or thelike, at a selected site in the body of a user. The implantable glucosesensor set 10 includes a hollow, slotted insertion needle 14, and acannula 16. The needle 14 is used to facilitate quick and easysubcutaneous placement of the cannula 16 at the subcutaneous insertionsite. The cannula 16 includes a sensing portion 18 of the sensor 12 toexpose one or more sensor electrodes 20 to the user's bodily fluidsthrough a window 22 formed in the cannula 16. After insertion, theinsertion needle 14 is withdrawn to leave the cannula 16 with thesensing portion 18 and the sensor electrodes 20 in place at the selectedinsertion site.

In preferred embodiments, the implantable subcutaneous glucose sensorset 10 facilitates accurate placement of a flexible thin filmelectrochemical sensor 12 of the type used for monitoring specific bloodparameters representative of a user's condition. Preferably, the sensor12 monitors blood glucose levels, and may be used in conjunction withautomated or semi-automated medication infusion pumps of the external orimplantable type as described in U.S. Pat. Nos. 4,562,751; 4,678,408;4,685,903 or 4,573,994, to deliver insulin to a diabetic patient.However, other embodiments may monitor other analytes to determine viralload, HIV activity, bacterial levels, cholesterol levels, medicationlevels, or the like.

Preferred embodiments of the flexible electrochemical sensor 12 areconstructed in accordance with thin film mask techniques to includeelongated thin film conductors embedded or encased between layers of aselected insulative material such as polyimide film or sheet. The sensorelectrodes 20 at a tip end of the sensing portion 18 are exposed throughone of the insulative layers for direct contact with patient blood, orother bodily fluids, when the sensor 12 is subcutaneously placed at aninsertion site. The sensing portion 18 is joined to a connection portion24 (see FIG. 2) that terminates in conductive contact pads, or the like,which are also exposed through one of the insulative layers. Inalternative embodiments, other types of implantable glucose sensors,such as chemical based, optical based, or the like, may be used.

As is known in the art, and illustrated schematically in FIG. 2, theconnection portion 24 and the contact pads are generally adapted for adirect wired electrical connection to a suitable sensor monitor formonitoring a user's condition in response to signals derived from thesensor electrodes 20. Further description of flexible thin film sensorsof this general type are be found in U.S. Pat. No. 5,391,250, entitledMETHOD OF FABRICATING THIN FILM SENSORS, which is herein incorporated byreference. The connection portion 24 may be conveniently connectedelectrically to the sensor monitor (not shown), a glucose monitor 100,or a data processor 200, computer, communication station, or the like,by a connector block 28 (or the like) as shown and described in U.S.Pat. No. 5,482,473, entitled FLEX CIRCUIT CONNECTOR, which is alsoherein incorporated by reference. Thus, in accordance with embodimentsof the present invention, subcutaneous sensor sets 10 are configured orformed to work with either a recording, wired or a wireless system.

The sensor 12 is mounted in a mounting base 30 adapted for placementonto the skin of a user. As shown, the mounting base 30 is a generallyrectangular pad having an underside surface coated with a suitablepressure sensitive adhesive layer 32, with a peel-off paper strip 34normally provided to cover and protect the adhesive layer 32, until thesensor set 10 is ready for use. As shown in FIGS. 1 and 2, the mountingbase 30 includes upper and lower layers 36 and 38, with the connectionportion 24 of the flexible sensor 12 being sandwiched between the layers36 and 38. The connection portion 24 has a forward section joined to thesensing portion 18 of the sensor 12, which is folded angularly to extenddownwardly through a bore 40 formed in the lower base layer 38. Inpreferred embodiments, the adhesive layer 32 includes an anti-bacterialagent to reduce the chance of infection; however, alternativeembodiments may omit the agent. In further alternative embodiments, themounting base may be other shapes, such as circular, oval, hour-glass,butterfly or the like.

The insertion needle 14 is adapted for slide-fit reception through aneedle port 42 formed in the upper base layer 36 and further through thelower bore 40 in the lower base layer 38. As shown, the insertion needle14 has a sharpened tip 44 and an open slot 46 which extendslongitudinally from the tip 44 at the underside of the needle 14 to aposition at least within the bore 40 in the lower base layer 36. Abovethe mounting base 30, the insertion needle 14 may have a full roundcross-sectional shape, and may be closed off at a rear end of the needle14. Further description of the needle 14 and the sensor set 10 are foundin U.S. Pat. No. 5,586,553, entitled “TRANSCUTANEOUS SENSOR INSERTIONSET” and co-pending U.S. patent application Ser. No. 09/346,835 filedJul. 2, 1999, entitled “INSERTION SET FOR A TRANSCUTANEOUS SENSOR,”which are herein incorporated by reference.

The cannula 16 is best shown in FIGS. 6 and 7, and includes a firstportion 48 having partly-circular cross-section to fit within theinsertion needle 14 that extends downwardly from the mounting base 30.In alternative embodiments, the first portion 48 may be formed with asolid core; rather than a hollow core. In preferred embodiments, thecannula 16 is constructed from a suitable medical grade plastic orelastomer, such as polytetrafluoroethylene, silicone, or the like. Thecannula 16 also defines an open lumen 50 in a second portion 52 forreceiving, protecting and guideably supporting the sensing portion 18 ofthe sensor 12. The cannula 16 has one end fitted into the bore 40 formedin the lower layer 38 of the mounting base 30, and the cannula 16 issecured to the mounting base 30 by a suitable adhesive, ultrasonicwelding, snap fit or other selected attachment method. From the mountingbase 30, the cannula 16 extends angularly downwardly with the firstportion 48 nested within the insertion needle 14, and terminatesslightly before the needle tip 44. At least one window 22 is formed inthe lumen 50 near the implanted end 54, in general alignment with thesensor electrodes 20, to permit direct electrode exposure to the user'sbodily fluid when the sensor 12 is subcutaneously placed.

As shown in FIGS. 1 and 2, the glucose monitor 100 is coupled to asubcutaneous glucose sensor set 10 by a cable 102 through a connector104 that is electrically coupled to the connector block 28 of theconnector portion 24 of the subcutaneous glucose sensor set 10. Inpreferred embodiments, the plug connector 103 of the cable 102 isconnected to the glucose monitor 100 through a plug receptacle 105. Inalternative embodiments, the cable 102 may be omitted, and the glucosemonitor 100 may include an appropriate connector (not shown) for directconnection to the connector portion 24 of the subcutaneous glucosesensor set 10 or the subcutaneous glucose sensor set 10 may be modifiedto have the connector portion 24 positioned at a different location,such as for example, the top of the subcutaneous sensor set 10 tofacilitate placement of the telemetered characteristic monitortransmitter over the subcutaneous sensor set 10. This would minimize theamount of skin surface covered or contacted by medical devices, and tendto minimize potential electrical interference induced by movement of thesubcutaneous glucose sensor set 10 relative to the telemeteredcharacteristic monitor transmitter 100. In further alternativeembodiments, the cable 102 and the connector 104 may be formed as add-onadapters to fit different types of connectors on different types orkinds of sensor sets. The use of adapters would facilitate adaptation ofthe glucose monitor 100 to work with a wide variety of sensor systems.

The glucose monitor 100 includes a housing 106 that supports a printedcircuit board 108, batteries 110, memory storage 112, the cable 102 withthe plug connector 103, and the plug receptacle 105. In preferredembodiments, the housing 106 is formed from an upper case 114 and alower case 116 that are sealed with an ultrasonic weld to form awaterproof (or resistant) seal to permit cleaning by immersion (orswabbing) with water, cleaners, alcohol or the like. In preferredembodiments, the upper and lower case 114 and 116 are formed from amedical grade plastic. However, in alternative embodiments, the uppercase 114 and lower case 116 may be connected together by other methods,such as snap fits, sealing rings, RTV (silicone sealant) and bondedtogether, or the like, or formed from other materials, such as metal,composites, ceramics, or the like. In preferred embodiments, the housing106 is generally rectangular. However, in alternative embodiments, othershapes, such as hour glass, disk, oval shaped, or the like, may be used.Preferred embodiments of the housing 106 are sized in the range of 3.0square inches by 0.5 inches thick. However, larger or smaller sizes,such as 0.5 square inches and 0.15 inches thick or less, and 5.0 squareinches and 1.0 inches thick or more, may be used.

As shown, the lower case 116 may have an underside surface that includesa belt clip 118 (or the like) to attach to a user's clothing. In otherembodiments, the underside surface is coated with a suitable pressuresensitive adhesive layer, with a peel-off paper strip normally providedto cover and protect the adhesive layer, until the glucose monitor 100is ready for use. In preferred embodiments, the adhesive layer includesan anti-bacterial agent to reduce the chance of infection; however,alternative embodiments may omit the agent. In further alternativeembodiments, the glucose monitor 100 is secured to the body by othermethods, such as an adhesive overdressing, straps, belts, clips or thelike.

In preferred embodiments, the cable 102 should also include a flexiblestrain relief portion (not shown) to minimize strain on the subcutaneoussensor set 10 and prevent movement of the implanted sensor 12, which canlead to discomfort or dislodging of the glucose sensor set 10. Theflexible strain relief portion is intended to minimize sensor artifactsgenerated by user movements that causes the subcutaneous glucose sensorset 10 to move relative to the glucose monitor 100.

The interface via the plug receptacle 105 of the glucose monitor 100connects with the cable plug 103 of the cable 102 that is connected withthe subcutaneous sensor set 10 via the connector 104. In preferredembodiments, the sensor interface may be configured in the form of ajack to accept different types of cables that provide adaptability ofthe glucose monitor 100 to work with different types of subcutaneousglucose sensors and/or glucose sensors placed in different locations ofthe user's body. However, in alternative embodiments, the sensorinterface is permanently connected to the cable 102. In preferredembodiments, the printed circuit board 108, and associated electronics,are capable of operating in a temperature range of 0° C. and 50° C.However, larger or smaller temperature ranges may be used.

Preferably, the battery assembly will use a weld tab design to connectpower to the system. For example, it can use three series silver oxide357 battery cells 110, or the like. However, it is understood thatdifferent battery chemistries may be used, such as lithium, alkaline orthe like, and different numbers of batteries can be used. In furtherembodiments, the sensor interface will include circuitry and/or amechanism for detecting connection to the subcutaneous glucose sensorset 10. This would provide the capability to save power and to morequickly and efficiently start initialization of the subcutaneous glucosesensor set 10. In preferred embodiments, the batteries 110 have a lifein the range of 3 months to 2 years, and provide a low battery warningalarm. Alternative embodiments, may provide longer or shorter batterylifetimes, or include a power port or solar cells to permit rechargingof the batteries 110 in the glucose monitor 100.

In preferred embodiments, the glucose monitor 100 provides power,through plug receptacle 105 to the cable plug 103 of the cable 102 andthen through the cable connector 104 to the glucose sensor set 10. Thepower is used to drive the glucose sensor set 10. The power connectionis also used to speed the initialization of the sensor 12, when it isfirst placed under the skin. The use of an initialization process canreduce the time for sensor 12 stabilization from several hours to anhour or less. The preferred initialization procedure uses a two stepprocess. First, a high voltage (preferably between 1.0-1.2volts—although other voltages may be used) is applied to the sensor 12for 1 to 2 minutes (although different time periods may be used) toallow the sensor 12 to stabilize. Then, a lower voltage (preferablybetween 0.5-0.6 volts—although other voltages may be used) is appliedfor the remainder of the initialization process (typically 58 minutes orless). Other stabilization/initialization procedures using differingcurrents, currents and voltages, different numbers of steps, or thelike, may be used. Other embodiments may omit theinitialization/stabilization process, if not required by the glucosesensor or if timing is not a factor.

At the completion of the stabilizing process, an initial reading may bedownloaded from the glucose sensor set 10 and the glucose monitor 100 tothe data processor 200, computer, communication station, or the like, toverify proper operation of the glucose sensor 10 and the glucose monitor100. In alternative embodiments, a fluid containing a known value ofglucose may be injected into the site around the glucose sensor set 10,and then the reading sent to the glucose monitor 100 records the datafor the known value to provide a reference point to the recorded data,such as disclosed in U.S. patent application Ser. No. 09/161,128, filedSep. 25, 1998, entitled “A SUBCUTANEOUS IMPLANTABLE SENSOR SET HAVINGTHE CAPABILITY TO REMOVE OR DELIVER FLUIDS TO AN INSERTION SITE,” nowU.S. Pat. No. 5,951,521, which is herein incorporated by reference.During the stabilization process, the glucose monitor 100 checks todetermine if the glucose sensor set 10 is still connected. If theglucose sensor set 10 is no longer connected, the glucose monitor 100will abort the stabilization process and sound an alarm (or flash alight, or download a signal to the data processor 200, computer,communication station, or the like, to sound an alarm).

In further alternative embodiments, the glucose monitor 100 can becombined with a glucose sensor set 10 as a single unit. This would beparticularly well adapted where batteries and the glucose monitor 100can be made cheaply enough to facilitate changing the glucose monitor100 with each new glucose sensor set 10, such as in a Holter-typemonitor, or the like.

As shown in FIG. 2, the data processor 200, computer, communicationstation, or the like, may include a display 214 that is used to displaythe results of the measurement received from the sensor 18 in theglucose sensor set 10 received via a download from the glucose monitor100. The results and information displayed includes, but is not limitedto, trending information of the characteristic (e.g., rate of change ofglucose), graphs of historical data, average characteristic levels(e.g., glucose), or the like. Alternative embodiments include theability to scroll through the data. The display 214 may also be usedwith buttons (not shown) on the data processor 200, computer,communication station, or the like, characteristic monitor to program orupdate data in the data processor 200. In preferred embodiments, theglucose monitor 100 includes a display 132 to assist the user inprogramming the glucose monitor 100, entering data, stabilizing,calibrating, downloading data, or the like.

In further embodiments of the present invention, the data processor 200,computer, communication station, or the like, may be replaced by adifferent device. For example, in one embodiment, the glucose monitor100 communicates with an RF programmer (not shown) that is also used toprogram and obtain data from an infusion pump or the like. The RFprogrammer may also be used to update and program the glucose monitor100, if the glucose monitor 100 includes a receiver for remoteprogramming, calibration or data receipt. The RF programmer can be usedto store data obtained from the sensor 18 and then provide it to eitheran infusion pump, characteristic monitor, computer or the like foranalysis. In further embodiments, the glucose monitor 100 may transmitthe data to a medication delivery device, such as an infusion pump orthe like, as part of a closed loop system. This would allow themedication delivery device to compare sensor results with medicationdelivery data and either sound alarms when appropriate or suggestcorrections to the medication delivery regimen. In preferredembodiments, the glucose monitor 100 would include a transmitter toreceive updates or requests for additional sensor data. An example ofone type of RF programmer can be found in U.S. patent application Ser.No. 09/334,858 filed Jun. 17, 1999 and is entitled “INFUSION DEVICE WITHREMOTE PROGRAMMING, CARBOHYDRATE CALCULATOR AND/OR VIBRATION ALARMCAPABILITIES,” which is herein incorporated by reference.

Additional embodiments of the present invention may include a vibratoralarm (or optical indicator such as an L.E.D.) in the either, or both,the glucose monitor 100 to provide a tactile (vibration) alarm to theuser, so as to indicate a glucose sensor set malfunction, improperconnection, low battery, missed message, bad data, interference, or thelike. The use of a vibration alarm provides additional reminders to anaudio alarm, which could be important with someone suffering an acutereaction, or to have non-audio alarms to preserve and conceal thepresence of the glucose monitor.

While the description above refers to particular embodiments of thepresent invention, it will be understood that many modifications may bemade without departing from the spirit thereof The accompanying claimsare intended to cover such modifications as would fall within the truescope and spirit of the present invention.

The presently disclosed embodiments are therefore to be considered inall respects as illustrative and not restrictive, the scope of theinvention being indicated by the appended claims, rather than theforegoing description, and all changes which come within the meaning andrange of equivalency of the claims are therefore intended to be embracedtherein.

What is claimed is:
 1. A glucose sensor package system for sterilizing aglucose sensor using electron beam sterilization, the system comprising:at least one glucose sensor; a protective package having an interior tohold the at least one glucose sensor in the interior of the protectivepackage; and at least one radiation exposure indicator to determine ifthe protective package has been exposed to a predetermined exposurelevel of electron beam sterilization.
 2. The glucose sensor packagesystem according to claim 1, wherein the predetermined exposure level isabove 2.0 Mrad.
 3. The glucose sensor package system according to claim1, wherein the predetermined exposure level is less than or equal to 5.0Mrad.
 4. The glucose sensor package system according to claim 1, whereinthe predetermined temperature is above 0.5 Mrad.
 5. The glucose sensorpackage system according to claim 1 wherein the at least one radiationexposure indicator indicates that the predetermined exposure levelexisted for a period of time.
 6. The glucose sensor package systemaccording to claim 1, wherein the at least one radiation exposureindicator is attached to the protective package.
 7. The glucose sensorpackage system according to claim 6, wherein the at least one radiationexposure indicator is attached to the interior of the protectivepackage.
 8. The glucose sensor package system according to claim 6,wherein the at least one radiation exposure indicator is attached to anexterior of the protective package.
 9. The glucose sensor package systemaccording to claim 1, wherein the at least one radiation exposureindicator is contained within the protective package.
 10. The glucosesensor package system according to claim 1, wherein the at least oneradiation exposure indicator is attached to the glucose sensor.
 11. Theglucose sensor package system according to claim 1, wherein the at leastone radiation exposure indicator is a sticker.
 12. A method ofsterilizing a glucose sensor using electron beam sterilization, themethod comprising the steps of: providing at least one glucose sensor;providing protective package having an interior; holding the at leastone glucose sensor in the interior of the protective package; and usingat least one radiation exposure indicator to determine if the protectivepackage has been exposed to a predetermined exposure value.
 13. Themethod according to claim 12, wherein the predetermined exposure valueis 2 Mrads.
 14. The method according to claim 12, wherein thepredetermined exposure value is less than or equal to 5 Mrads.
 15. Themethod according to claim 12, wherein the predetermined exposure valueis above 0.5 Mrads.
 16. The method according to claim 12, further usingthe at least one radiation exposure indicator to indicate that thepredetermined exposure value existed for a period of time.
 17. Themethod according to claim 12, further comprising the step of attachingthe at least one radiation exposure indicator to the protective package.18. The method according to claim 17, further comprising the step ofattaching the at least one radiation exposure indicator to the interiorof the protective package.
 19. The method according to claim 17 furthercomprising the step of attaching the at least one radiation exposureindicator to an exterior of the protective package.
 20. The methodaccording to claim 12, further comprising the step of containing the atleast one radiation exposure indicator within the protective package.21. The method according to claim 12, further comprising the step ofattaching the at least one radiation exposure indicator to the glucosesensor.
 22. The method according to claim 12, further comprising usingthe at least one radiation exposure indicator formed as a sticker.